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- W3083006907 abstract "Podocytes are highly specialized cells that play an essential role in maintaining the integrity and function of the glomerular filtration barrier. Wilms tumor 1 (WT1) and β-catenin are two master regulators that play opposing roles in podocyte biology and mutually antagonize each other. However, exactly how β-catenin inhibits WT1 remains incompletely understood. In this study, we demonstrated the role of miR-466o-3p in mediating β-catenin-triggered podocyte injury by targeting WT1. The expression of miR-466o-3p was upregulated in cultured podocytes after β-catenin activation and in glomerular podocytes in adriamycin (ADR) nephropathy, remnant kidney after 5/6 renal ablation, and diabetic kidney disease. Bioinformatics analysis and luciferase reporter assay confirmed that miR-466o-3p directly targeted WT1 mRNA. Furthermore, overexpression of miR-466o-3p downregulated WT1 protein and promoted podocyte injury in vitro. Conversely, inhibition of miR-466o-3p alleviated β-catenin-induced podocyte dysfunction. In mouse model of ADR nephropathy, overexpression of miR-466o-3p inhibited WT1, aggravated podocytes injury and deteriorated proteinuria. In contrast, inhibition of renal miR-466o-3p by antagomiR, either prior to or after ADR injection, substantially restored WT1, alleviated podocytes injury and reduced renal fibrosis. These studies reveal a critical role for miR-466o-3p, a novel microRNA that has not been characterized previously, in mediating β-catenin-triggered WT1 inhibition. Our findings also uncover a new pathogenic mechanism by which β-catenin promotes podocyte injury and proteinuria in glomerular diseases." @default.
- W3083006907 created "2020-09-11" @default.
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- W3083006907 date "2020-09-05" @default.
- W3083006907 modified "2023-10-17" @default.
- W3083006907 title "MicroRNA‐466o‐3p mediates β‐catenin‐induced podocyte injury by targeting Wilms tumor 1" @default.
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- W3083006907 doi "https://doi.org/10.1096/fj.202000464r" @default.
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